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Empty drops in scRNA-seq uncover the surprising prevalence of sequestered neuropeptide mRNA and pervasive sequencing artifacts

Gorin, G.; Goodman, L.

2026-02-15 bioinformatics
10.64898/2026.02.13.705850 bioRxiv
Show abstract

The empty drops in single-cell sequencing experiments are an underexplored resource. As such, they present a substrate to ask questions orthogonal to standard single-cell sequencing workflows, calibrate statistical models using simple internal controls, and detect technical outliers which would be otherwise challenging to distinguish from real biology. In this case study, we report a relatively simple procedure to detect sequencing artifacts and make recommendations to reduce the risk of erroneous quantifications. In addition, we report the surprising abundance and co-expression of mRNA coding for neuropeptide-related genes in the empty drops, possibly reflecting underlying physiology.

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